Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis

Key Points

  • Listeria monocytogenes is a food-borne pathogen that primarily afflicts immunocompromised individuals and can provoke septicaemia, meningitis and fetal infection or abortion in infected pregnant women.

  • L. monocytogenes is an excellent model for intracellular infection, as it mediates its own uptake into non-phagocytic cells, subsequently escapes from the vacuole, polymerizes actin to spread from cell to cell and secretes factors that alter transcription, post-translational modifications, innate immune signalling and cytoskeletal rearrangements.

  • L. monocytogenes can traverse three distinct epithelial barriers and competes for a niche in the dense intestinal microbiota through upregulation of metabolic pathways and the secretion of toxic bactericidal factors.

  • L. monocytogenes utilizes a plethora of complex regulation strategies such as riboregulators and small non-coding RNAs to quickly adapt to and thrive in highly divergent physiological contexts.

Abstract

Listeria monocytogenes is a food-borne pathogen responsible for a disease called listeriosis, which is potentially lethal in immunocompromised individuals. This bacterium, first used as a model to study cell-mediated immunity, has emerged over the past 20 years as a paradigm in infection biology, cell biology and fundamental microbiology. In this Review, we highlight recent advances in the understanding of human listeriosis and L. monocytogenes biology. We describe unsuspected modes of hijacking host cell biology, ranging from changes in organelle morphology to direct effects on host transcription via a new class of bacterial effectors called nucleomodulins. We then discuss advances in understanding infection in vivo, including the discovery of tissue-specific virulence factors and the 'arms race' among bacteria competing for a niche in the microbiota. Finally, we describe the complexity of bacterial regulation and physiology, incorporating new insights into the mechanisms of action of a series of riboregulators that are critical for efficient metabolic regulation, antibiotic resistance and interspecies competition.

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Figure 1: Overview of Listeria monocytogenes infection.
Figure 2: Entry of Listeria monocytogenes into cells.
Figure 3: Intestinal invasion and interaction of Listeria monocytogenes with the microbiota.
Figure 4: RNA regulation and miniproteins in Listeria monocytogenes.

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Acknowledgements

The authors apologize to those colleagues whose work could not be included owing to space constraints. The authors gratefully acknowledge financial support from the European Research Area Network (ERA-NET) Infect-ERA BACVIRISG15 and PROANTILIS, the European Research Council (ERC) Advanced Grant BacCellEpi (670823), Agence Nationale de la Recherche (ANR) BACNET (10-BINF-02-01), ANR Investissement d'Avenir Programme (10-LABX-62-IBEID), Human Frontier Science Program (HFSP; RGP001/2013), the Balzan Foundation, the Pasteur-Weizmann Council and the Fondation le Roch les Mousquetaires. The authors thank D. Ribet, J.J. Quereda, S. Brisse and M. Lecuit for allowing us to adapt their figures. The authors thank H. Bierne, J. Pizarro-Cérda and O. Dussurget for helpful discussions. L.R. is supported by an HFSP long-term fellowship. P.C. is a senior international research scholar of the Howard Hughes Medical Institute, USA.

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L.R. and P.C. researched the data for the article, wrote the article, provided a substantial contribution to discussions of the content and reviewed and edited the manuscript before submission.

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Correspondence to Lilliana Radoshevich or Pascale Cossart.

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Glossary

Actin nucleation

The assembly of monomeric actin into filaments by actin nucleators, which can result in branched or linear actin filaments depending on the actin nucleator.

Actin-based motility

Listeria monocytogenes-mediated motility co-opts cellular actin nucleators to form bundles of actin that propel the bacterium within the cell and allow it to spread from one cell to another.

Receptor-mediated endocytosis

Cellular uptake of host surface receptors to regulate growth factor signalling or receptor turnover; the process requires monoubiquitylation of the receptor, clathrin and actin.

Internalin

A Listeria monocytogenes protein characterized by leucine-rich repeat domains that can be anchored to the bacterial cell wall by a sorting motif or secreted.

Vacuolar rupture

Vacuolar damage (or phagosomal damage in phagocytic cells) by bacterial virulence factors that allow bacterial escape into the cytosol.

Phage excision

The active process of removal of DNA from a lysogenic (non-lytic) bacteriophage that was previously integrated into the bacterial genome.

LC3-mediated phagocytosis

Phagocytosis in which the autophagy microtubule-associated protein light-chain 3 (LC3) is conjugated to the lipid phosphatidylethanolamine on the inside of the plasma membrane.

Mitochondrial fission

Mitochondrial division mediated by dedicated cellular factors called dynamin-related protein 1 (DRP1 and mitochondrial fission factor (Mff).

Unfolded protein response

(UPR.) When the protein folding demand of the endoplasmic reticulum (ER) exceeds its capacity, this response upregulates chaperones, blocks translation into the ER and increases ER folding capacity.

Cathepsins

A class of proteases that degrade other proteins and are typically activated by the acidic conditions in the lysosome.

Nucleomodulins

A class of bacterial virulence factors that are expressed in the cytoplasm and travel to the nucleus where they can affect host transcription.

Bromo adjacent homology domain-containing 1 protein

(BAHD1). A protein that is part of a transcriptional repression complex that affects the expression of interferon-stimulated genes following Listeria monocytogenes infection.

Clathrin

A protein that is important in endocytosis and exocytosis and has heavy chain variants and light chain variants that form a polyhedral lattice on the surface of vesicles.

Sumoylation

The process by which a small ubiquitin-like modifier covalently binds to its substrates. This typically leads to changes in localization or sequestration of transcription factors resulting in transcriptional repression.

Formins

A family of proteins that polymerize actin; each formin can have distinct actin-nucleating properties depending on the family.

Diaphanous formins

A subset of formins that have an autoinhibitory domain that is released by binding to GTPases.

Efferocytosis

The process for phagocytosing dead or dying cells that is initiated by the recognition of phosphatidylserine lipids on the cell surface (lipids normally present on the internal side of the plasma membrane).

Autophagy

A catabolic process that can nonspecifically or selectively capture cytosolic contents, organelles or invading pathogens and target them for degradation in the lysosome.

Necroptosis

A programmed cell death process, distinct from apoptosis, which generates inflammatory signals and typically occurs during infection.

Trophoblasts

Cells that will form the placenta, which are derived from fetal tissue and form the external layer of the developing blastocyst in the context of pregnancy.

Gnotobiotic

A condition in which the precise contents of the microbiota (bacteria and other microorganisms) of an animal are known; can refer to zero bacteria (germ-free) or a known subset of bacteria.

Immune priming

Transcriptional activation of innate defence pathways or immune memory pathways that leads to a subsequent downstream immune response that is more pronounced than the initial naive immune response.

ANTAR element

An RNA-binding domain called AmiR and NasR transcriptional anti-terminator regulator (ANTAR).

Attenuation-like mechanism

A mechanism of transcriptional control in bacteria and archaea that incorporates a terminator sequence into the 5′ mRNA leader that can stall the ribosome (resulting in aborted translation) or allow readthrough depending on metabolic conditions.

Ribosomal stalling

An event that occurs when the ribosome slows during translation, often owing to a specific secondary structure in the mRNA, resulting in aborted translation or temporary ribosomal pausing.

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Radoshevich, L., Cossart, P. Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis. Nat Rev Microbiol 16, 32–46 (2018). https://doi.org/10.1038/nrmicro.2017.126

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